Methodology for Identification of Cysteine-Reactive Covalent Inhibitors
Covalent fragments are an emerging technology to discover covalent ligands in target-based or phenotypic screens. Here we describe screening of cysteine-reactive covalent fragments against a protein of interest using mass spectrometry or enzymatic methods.
Key wordsCovalent fragments Cysteine
Funding was provided from Northwestern University (A.V.S.), Pew Charitable Trusts (A.V.S.), National Institutes of Health Grants R01GM115632 (A.V.S.), T32GM105538 (S.G.K.), and the ACS Medicinal Chemistry Predoctoral Fellowship (S.G.K.). We thank Rama Mishra and the Center for Molecular Innovation and Drug Discovery for assisting with the initial design of the library of electrophilic fragments.
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